Synthesis, cytotoxic, anti-lipoxygenase and anti-acetylcholinesterase capacities of novel derivatives from harmine

Figures & data

Scheme 1. Synthesis of hydrazones 4a–j.

Scheme 2. Synthesis of derivatives 5a–c.

Table 1. Effect of microwave irradiation for the synthesis of 1,2,3-triazoles 7a–f.

		Conventional heating^a		Microwave irradiation^b
Entry	R	Time (h)	Yield (%)	Time (min)	Yield (%)
7a	H	24	65	5	78
7b	CH3	48	50	5	65
7c	OCH3	48	70	7	80
7d	Cl	–	–	5	70
7e	NO2	24	80	5	90
7f	C2H5	–	–	7	60

a Reflux.

b 200 W, 100 °C.

Scheme 3. Synthesis of triazoles7a–f.

Table 2. MCF-7, HCT-116 and OVCAR-3 inhibitions (IC₅₀ μM) of harmine 1 and its derivatives expressed as IC₅₀ (μM)^a.

Compounds	MCF-7	HCT-116	OVCAR-3
1	1.3 ± 0.2^b	0.7 ± 0.03^b	18.0 ± 2.0^b
2	>100	36.0 ± 2.0	53.0 ± 3.0
3	>100	>100	>100
4a	4.0 ± 0.0	5.0 ± 0	2.5 ± 0.1
4b	>100	>100	>100
4c	>100	25.0 ± 4.0	23.7 ± 1.4
4d	4.5 ± 0.0	25.0 ± 2.0	14.0 ± 1.0
4e	4.0 ± 0.6	2.9 ± 0.4	27.3 ± 1.0
4f	27.0 ± 4.0	18.0 ± 2.0	6.4 ± 0.8
4g	2.8 ± 0.2	3.0 ± 0.3	16.7 ± 0.7
4h	18.0 ± 2.0	>100	71.0 ± 9.0
4i	87.0 ± 11.0	3.8 ± 0.5	20.0 ± 1.7
4j	11.0 ± 1.0	7.0 ± 0.0	22.0 ± 2.0
5a	>100	>100	>100
5b	>100	>100	>100
5c	>100	>100	>100
6	63.0 ± 5.0	25.0 ± 2.0	9.0 ± 1.0
7a	6.3 ± 0.7	40.0 ± 5.0	96.0 ± 8.0
7b	32.0 ± 2.0	31.0 ± 4.0	>100
7c	43.0 ± 3.0	43.0 ± 6.0	>100
7d	29.0 ± 2.0	27.0 ± 3.0	>100
7e	54.0 ± 7.0	52.0 ± 7.0	>100
7f	41.0 ± 3.0	42.0 ± 5.0	>100
Doxorubicin	0.38 ± 0.03	0.36 ± 0.03	–
Tamoxifen	–	–	0.52 ± 0.04

a Averages ± SD were obtained from three different experiments.

b Results obtained in our previous work38.

Table 3. Acetylcholinesterase and 5-lipoxygenase inhibition capacity of harmine 1 and its derivatives expressed as IC₅₀ (μM)^a.

Compound	Acetylcholinesterase	5-Lipoxygenase
1	10.4 ± 0.4^b	>100^b
2	23.9 ± 1.2	31.6 ± 2.4
3	44.6 ± 3.2	30.9 ± 1.9
4a	>100	>100
4b	>100	39.8 ± 1.1
4c	>100	63.1 ± 3.1
4d	>100	>100
4e	>100	>100
4g	>100	>100
4h	>100	53.7 ± 4.3
4i	>100	>100
4j	>100	>100
5a	>100	>100
5b	>100	>100
5c	>100	>100
6	1.9 ± 1.5^b	28.2 ± 2.1
7a	>100	>100
7b	>100	>100
7c	>100	>100
7d	>100	>100
7e	>100	>100
7f	>100	>100
Galantamine	4.1 ± 0.2	–
NDGA	–	8.1 ± 0.1

a Averages ± SD were obtained from three different experiments.

b Results obtained in our previous work38.

Katrusiak A, Katrusiak A. One-step ring condensation of hydrazine derivatives and cyclic anhydrides. J Mol Struct 2015;1085:28–36

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